Stimulation of cannabinoid receptor 2 (CB<sub>2</sub>) suppresses microglial activation
<p>Abstract</p> <p>Background</p> <p>Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), and HIV dementia. It is well known that inflammatory mediators such as nitr...
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Series: | Journal of Neuroinflammation |
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doaj-07a711c4eb1c41268a929d34adc108b92020-11-25T02:14:54ZengBMCJournal of Neuroinflammation1742-20942005-12-01212910.1186/1742-2094-2-29Stimulation of cannabinoid receptor 2 (CB<sub>2</sub>) suppresses microglial activationFernandez FranciscoKlein ThomasBai YunSun NanHou HuayanMori TakashiObregon DemianEhrhart JaredTan JunShytle R<p>Abstract</p> <p>Background</p> <p>Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO), cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation <it>in vitro </it>and <it>in vivo </it>through stimulation of cannabinoid receptor 2 (CB<sub>2</sub>).</p> <p>Methods</p> <p>In this study, we investigated the effects of a cannabinoid agonist on CD40 expression and function by cultured microglial cells activated by IFN-γ using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB<sub>2 </sub>small interfering RNA (siRNA) analyses. Furthermore, we examined if the stimulation of CB<sub>2 </sub>could modulate the capacity of microglial cells to phagocytise Aβ<sub>1–42 </sub>peptide using a phagocytosis assay.</p> <p>Results</p> <p>We found that the selective stimulation of cannabinoid receptor CB<sub>2 </sub>by JWH-015 suppressed IFN-γ-induced CD40 expression. In addition, this CB<sub>2 </sub>agonist markedly inhibited IFN-γ-induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-α and nitric oxide production induced either by IFN-γ or Aβ peptide challenge in the presence of CD40 ligation. Finally, we showed that CB<sub>2 </sub>activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Aβ<sub>1–42 </sub>peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB<sub>2 </sub>modulation in neurodegenerative diseases, particularly AD.</p> http://www.jneuroinflammation.com/content/2/1/29 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fernandez Francisco Klein Thomas Bai Yun Sun Nan Hou Huayan Mori Takashi Obregon Demian Ehrhart Jared Tan Jun Shytle R |
spellingShingle |
Fernandez Francisco Klein Thomas Bai Yun Sun Nan Hou Huayan Mori Takashi Obregon Demian Ehrhart Jared Tan Jun Shytle R Stimulation of cannabinoid receptor 2 (CB<sub>2</sub>) suppresses microglial activation Journal of Neuroinflammation |
author_facet |
Fernandez Francisco Klein Thomas Bai Yun Sun Nan Hou Huayan Mori Takashi Obregon Demian Ehrhart Jared Tan Jun Shytle R |
author_sort |
Fernandez Francisco |
title |
Stimulation of cannabinoid receptor 2 (CB<sub>2</sub>) suppresses microglial activation |
title_short |
Stimulation of cannabinoid receptor 2 (CB<sub>2</sub>) suppresses microglial activation |
title_full |
Stimulation of cannabinoid receptor 2 (CB<sub>2</sub>) suppresses microglial activation |
title_fullStr |
Stimulation of cannabinoid receptor 2 (CB<sub>2</sub>) suppresses microglial activation |
title_full_unstemmed |
Stimulation of cannabinoid receptor 2 (CB<sub>2</sub>) suppresses microglial activation |
title_sort |
stimulation of cannabinoid receptor 2 (cb<sub>2</sub>) suppresses microglial activation |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2005-12-01 |
description |
<p>Abstract</p> <p>Background</p> <p>Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO), cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation <it>in vitro </it>and <it>in vivo </it>through stimulation of cannabinoid receptor 2 (CB<sub>2</sub>).</p> <p>Methods</p> <p>In this study, we investigated the effects of a cannabinoid agonist on CD40 expression and function by cultured microglial cells activated by IFN-γ using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB<sub>2 </sub>small interfering RNA (siRNA) analyses. Furthermore, we examined if the stimulation of CB<sub>2 </sub>could modulate the capacity of microglial cells to phagocytise Aβ<sub>1–42 </sub>peptide using a phagocytosis assay.</p> <p>Results</p> <p>We found that the selective stimulation of cannabinoid receptor CB<sub>2 </sub>by JWH-015 suppressed IFN-γ-induced CD40 expression. In addition, this CB<sub>2 </sub>agonist markedly inhibited IFN-γ-induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-α and nitric oxide production induced either by IFN-γ or Aβ peptide challenge in the presence of CD40 ligation. Finally, we showed that CB<sub>2 </sub>activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Aβ<sub>1–42 </sub>peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB<sub>2 </sub>modulation in neurodegenerative diseases, particularly AD.</p> |
url |
http://www.jneuroinflammation.com/content/2/1/29 |
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